ARV-471: Phase 2 VERITAC Trial Results November 22, 2022 Exhibit 99.1
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Agenda 3 Topic Participant Introduction John G. Houston, Ph.D. President and Chief Executive Officer, Arvinas ARV-471: VERITAC Clinical Data Update Ron Peck, M.D. Chief Medical Officer, Arvinas Conclusions John G. Houston, Ph.D. President and Chief Executive Officer, Arvinas Includes: Chris Boshoff, M.D., Ph.D. Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development ? Q&A
ARV-471: Potential best-in-class estrogen receptor- targeting therapy 4 Continued signals of efficacy across the Phase 1/2 trial in a patient population with 100% pretreatment with CDK4/6 inhibitors • To our knowledge, this is the most heavily pre-treated patient population evaluated with an ER-targeted therapy to date, and is expected to have highly ER-independent disease • In VERITAC: 100% prior CDK4/6i, 79% prior fulvestrant, and 73% prior chemo (45% in the metastatic setting) Clinical Benefit Rate (n)a December 2020 (Phase 1 dose escalation) 42% (5 of 12) December 2021 (Phase 1 dose escalation) 40% (19 of 47) December 2022 (Phase 2 cohort expansion [VERITAC]) 38% (71 of 71) In VERITAC, favorable tolerability at both 200 mg qd and 500 mg qd • No single TRAE in more than ~20% of patients • In 35 patients treated at 200mg (RP3D), no dose reductions and only 1 discontinuation • In this expansion cohort, no signal for bradycardia or visual disturbance Expect to begin two Ph 3 pivotal studies and in multiple ongoing combination and monotherapy studies with the potential position ARV-471 as the ER therapy of choice across ER+/HER2- breast cancer • 2L monotherapy Ph 3 to test patients with both ESR1-mutant tumors and all-comers (4Q 2022) • 1L combination Ph3 with palbociclib in patients without prior CDK4/6i (1Q 2023) aRate of confirmed complete response or partial response or stable disease ≥24 weeks CBR=clinical benefit rate; ER=estrogen receptor; ESR1=estrogen receptor 1 gene; PFS=progression-free survival; TRAE, treatment-related adverse events; RP3D, recommended Phase 3 dose; CDK, cyclin-dependent kinase
ARV-471: Potential to be the endocrine backbone of choice for ER+/HER2- breast cancer treatment 5 Potential Future US ER+/HER2- Breast Cancer Treatment Paradigm with ARV-471 Adjuvant (Post-Surgical) Breast Cancer (~160K)* Metastatic Breast Cancer (~50K*) Second/Third LineFirst Line Endocrine Backbone Aromatase Inhibitors (AI) Fulvestrant or exemestane Add-on therapies CDK4/6 and other targeted inhibitors mTOR inhibitors or PIK3 inhibitors Fulvestrant *U.S. incident population per year from SEER database CDK: cyclin-dependent kinases, Pi3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin Opportunity for ARV-471 Expansion Potential future state: ARV-471 Designed to be an oral, high-potency ER degrader with favorable safety profile Near-term
Studies with SERDs or ARV-471 Include a Wide Range of Prior Therapies VERITAC has most prior therapies among key studies PALOMA-31 Phase 3 study of palbociclib plus fulvestrant vs placebo plus fulvestrant (N=521) 0 0 34%‡ acelERA2 Phase 2 study of giredestrant vs SOC† (N=303) 42%* 19%* 32% SERENA-23 Phase 2 study of camizestrant vs fulvestrant (N=240) 50% 0 19% AMEERA-32 Phase 2 study of amcenestrant vs SOC† (N=290) 79%*,‡ 10%*,‡ 11%‡ VERONICA4 Phase 2 study of venetoclax plus fulvestrant vs fulvestrant (N=103) 100% 0 0 EMERALD5 Phase 3 study of elacestrant vs SOC† (N=477) 100% 30% 22% VERITAC Phase 2 expansion cohorts of ARV-471 (N=71) 100% 79% 45% 1Lancet Oncol 2016. 2ESMO 2022. 3San Antonio Breast Cancer Symposium 2022. 4Clin Cancer Res 2022..5J Clin Oncol 2022. *Advanced/metastatic setting. †Physician’s choice of fulvestrant or an aromatase inhibitor; tamoxifen also permitted in AMEERA-3. SOC=standard of care ‡Published data, manually calculated for overall population 6 E x p e c te d R e sista n c e E x p e c te d E ffic a c y
7 Ron Peck, M.D. Chief Medical Officer, Arvinas ARV-471: VERITAC Phase 2 Detailed Results
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 8 aEnrollment in the 200-mg QD cohort began before enrollment in the 500-mg QD cohort, bAnalyzed in patients enrolled ≥24 weeks prior to the data cutoff AE=adverse event; CBR=clinical benefit rate; CDK=cyclin-dependent kinase; CR=complete response; DOR=duration of response; ER=estrogen receptor; ESR1=estrogen receptor 1 gene; HER2=human epidermal growth factor receptor 2; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PK=pharmacokinetic; PR=partial response; QD=once daily; RECIST=Response Evaluation Criteria in Solid Tumors; SD=stable disease Phase 2 (VERITAC) Cohort Expansion Design Phase 2 cohort expansion (Part B; VERITAC) Key eligibility criteria • Histologically or cytologically confirmed ER+ and HER2- advanced breast cancer • Measurable or non-measurable disease per RECIST criteria v1.1 • ≥1 prior endocrine regimen (≥1 regimen for ≥6 months in the locally advanced or metastatic setting) • ≥1 prior CDK4/6 inhibitor • ≤1 prior chemotherapy regimen in the locally advanced or metastatic setting Primary endpoint • CBR (rate of confirmed CR or PR or SD ≥24 weeks)b Secondary endpoints • ORR, DOR, PFS, and OS • AEs and laboratory abnormalities • PK parameters Exploratory endpoints • ESR1 mutational status • ER protein levels ARV-471 200 mg orally QDa (n=35) ARV-471 500 mg orally QDa (n=36) Data cutoff date for this analysis • June 6, 2022
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. Patient Baseline Characteristics (VERITAC) 9 aBaseline ECOG PS status was unknown in 1 patient. bBaseline ESR1 status was unknown or missing in 5 patients; CDK=cyclin-dependent kinase; ECOG PS=Eastern Cooperative Oncology Group performance status; ESR1=estrogen receptor 1 gene Characteristic Total (N=71) Sex, n (%) Female 69 (97.2) Median age, y (range) 60 (41–86) ECOG PS, n (%)a 0 47 (66.2) 1 23 (32.4) Visceral disease, n (%) 39 (54.9) Sites of metastasis, n (%) Bone 49 (69.0) Liver 32 (45.1) Lung 17 (23.9) Other 5 (7.0) Characteristic Total (N=71) Baseline ESR1 status, n (%)b Mutant 41 (57.7) Wild-type 25 (35.2) Median no. of prior regimens (range) Any setting 4 (1–10) Metastatic setting 3 (0–7) Type of prior therapy, n (%) CDK4/6 inhibitor 71 (100) Aromatase inhibitor 64 (90.1) Fulvestrant 56 (78.9) Chemotherapy Any setting 52 (73.2) Metastatic setting 32 (45.1)
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 10 aRate of confirmed complete response or partial response or stable disease ≥24 weeks CBR=clinical benefit rate; ESR1=estrogen receptor 1 gene; QD=once daily Primary Endpoint: Clinical Benefit Ratea (VERITAC) 200 mg QD (n=35) 500 mg QD (n=36) Total (N=71) CBR, % (95% CI) 37.1 (21.5–55.1) 38.9 (23.1–56.5) 38.0 (26.8–50.3) Patients with mutant ESR1 (n=19) (n=22) (n=41) CBR, % (95% CI) 47.4 (24.4–71.1) 54.5 (32.2–75.6) 51.2 (35.1–67.1) • CBR consistent with Phase 1 dose escalation data • Phase 1: 40% in all patients, 50% in patients with ESR1-mutant tumors • Patients with WT ESR1 (n=25) exhibited CBR rate of 20%
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 11 aIncludes patients with measurable disease (n=44); 1 patient with measurable disease at baseline and PD as best overall response was excluded due to lack of complete set of target lesion measurements on-study bPatient had an unconfirmed partial response ESR1=estrogen receptor 1 gene; NE=not evaluable due to missing data for best overall response; PD=progressive disease; PR=confirmed partial response; QD=once daily; SD=stable disease Tumor Responsea (VERITAC) -100 -80 -60 -40 -20 0 20 40 60 80 100 120 B e s t % C h a n g e i n T a rg e t L e s io n D ia m e te r F ro m B a s e li n e 200 mg QD 500 mg QD P D P D P D P D P D P D P D P D P D P D S D S D P D S D S D S D P D P D P D P D S D S D S D S D S D S D S D P D S D N E S D P R P R S D b N E P D P D P D S D S D S D b S D b S D b S D b ESR1 mutation
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 100 80 60 40 20 0 Progression-Free Survivala (VERITAC) 12 aLimited follow-up in 500-mg QD cohort led to ≥50% of patients censored for PFS (curve not shown) ESR1=estrogen receptor 1 gene; mPFS=median progression-free survival; PFS=progression-free survival; QD=once daily All Patients 200 mg QD (n=35) Total (N=71) Events, n (%) 24 (68.6) 41 (57.7) mPFS, mo (95% CI) 3.5 (1.8–7.8) 3.7 (1.9–8.3) Mutant ESR1 200 mg QD (n=19) Total (n=41) Events, n (%) 12 (63.2) 22 (53.7) mPFS, mo (95% CI) 5.5 (1.8–8.5) 5.7 (3.6–9.4) 71 36 26 12 8 1 0 100 80 60 40 20 0 P F S P ro b a b il it y ( % ) 0 2 4 6 8 10 12 Time (months) No. at risk 35 18 13 8 5 1 0 Censored 200 mg QD Total Censored Mutant ESR1 200 mg QD Mutant ESR1 total P F S P ro b a b il it y ( % ) 0 2 4 6 8 10 12 Time (months) No. at risk 41 27 20 10 8 1 0 19 12 9 6 5 1 0
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. ER Degradationa With 200 mg QD ARV-471 (Phase 1/VERITAC) 13 aER immunoreactivity analyzed by QIF using the AQUA method, and ER positivity threshold derived by examining AQUA scores and visually inspecting all samples in the dataset to determine a cut point for ER positivity; ESR1 mutation status determined from tumor biopsy (n=1) or circulating tumor DNA (n=8) AQUA=automated quantitative analysis; ER=estrogen receptor; ESR1=estrogen receptor 1 gene; QD=once daily; QIF=quantitative immunofluorescence • Median ER degradation was 69% (range: 28%–95%) • Mean ER degradation was 71% Predose On-treatment 0 2000 4000 6000 E R A Q U A S c o re ER positivity threshold VERITAC patient Phase 1 patient Phase 1 patient Phase 1 patient VERITAC patient VERITAC patient Phase 1 patient VERITAC patient Phase 1 patient Solid line: ESR1 wild-type Dashed line: ESR1 mutation
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. Treatment-Emergent Adverse Event Summary (VERITAC) 14 aAcute respiratory failure in the setting of disease progression and unrelated to ARV-471 treatment bPatient had QT prolongation at baseline, received a concomitant QT-prolonging drug during ARV-471 treatment, and had hypokalemia cPatient had ECG T-wave abnormality at baseline ALT=alanine aminotransferase; ECG=electrocardiogram; QD=once daily; TEAE=treatment-emergent adverse event • Dose reductions due to TEAEs – 500-mg QD cohort (to 400 mg QD) • ALT increased (n=1) • Neutropenia (n=1) • Fatigue (n=1) • Discontinuations due to TEAEs – 200-mg QD cohort • QT prolongation (n=1)b – 500-mg QD cohort • ECG T-wave abnormality (n=1)c • Back pain/spinal cord compression (n=1) n (%) 200 mg QD (n=35) 500 mg QD (n=36) Total (N=71) TEAEs Any grade 32 (91) 30 (83) 62 (87) Grade 3/4 9 (26) 6 (17) 15 (21) Grade 5a 1 (3) 0 1 (1) Leading to discontinuation 1 (3) 2 (6) 3 (4) Leading to dose reduction 0 3 (8) 3 (4)
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 200 mg QD (n=35) 500 mg QD (n=36) Total (N=71) n (%) Grade 1 Grade 2 Grade 3/4a Grade 1 Grade 2 Grade 3/4b Grade 1 Grade 2 Grade 3/4 Any TRAE 13 (37) 13 (37) 2 (6) 11 (31) 9 (25) 3 (8) 24 (34) 22 (31) 5 (7) Fatigue 8 (23) 6 (17) 0 7 (19) 2 (6) 1 (3) 15 (21) 8 (11) 1 (1) Nausea 2 (6) 3 (9) 0 6 (17) 1 (3) 0 8 (11) 4 (6) 0 Arthralgia 4 (11) 0 0 5 (14) 0 0 9 (13) 0 0 Hot flush 6 (17) 0 0 1 (3) 0 0 7 (10) 0 0 AST increased 3 (9) 1 (3) 0 2 (6) 1 (3) 0 5 (7) 2 (3) 0 15 aGrade 3/4 TRAEs in the 200-mg QD cohort were grade 3 QT prolonged (n=1; same TEAE that led to discontinuation as shown in the prior slide) and grade 3 thrombocytopenia and grade 4 hyperbilirubinemia (n=1) bGrade 3/4 TRAEs in the 500-mg QD cohort were grade 3 fatigue, decreased appetite, and neutropenia (n=1 each) AST=aspartate aminotransferase; QD=once daily; TEAE=treatment-emergent adverse event; TRAE=treatment-related adverse event TRAEs Reported in ≥10% of Patients Overall (VERITAC)
San Antonio Breast Cancer Symposium®, December 6–10, 2022, Presentation GS3-03 This presentation is the intellectual property of the author/presenter. Contact them at SHurvitz@mednet.ucla.edu for permission to reprint and/or distribute. 16 aRate of confirmed complete response or partial response or stable disease ≥24 weeks AE=adverse event; BICR=blinded independent central review; CBR=clinical benefit rate; CDK=cyclin-dependent kinase; DOR=duration of response; ER=estrogen receptor; ESR1=estrogen receptor 1 gene; HER2=human epidermal growth factor receptor 2; ITT=intention to treat; ORR=overall response rate; OS=overall survival; QoL=quality of life; PFS=progression-free survival Phase 3 VERITAC-2 Trial • Women or men aged ≥18 years • Confirmed ER+/HER2- advanced breast cancer • 1 line of CDK4/6 inhibitor therapy in combination with endocrine therapy • ≤1 additional endocrine therapy • Most recent endocrine treatment given for ≥6 months prior to disease progression • No prior fulvestrant • No prior chemotherapy for locally advanced/metastatic disease • Radiological progression during or after the last line of therapy ARV-471 200 mg orally once daily Fulvestrant 500 mg intramuscularly days 1 and 15 of cycle 1 and day 1 of subsequent cycles Key eligibility criteria Primary endpoint • PFS by BICR in – ITT population – ESR1 mutant population Secondary endpoints include: • OS, ORR, DOR, and CBRa • AEs • QoL measurements R A N D O M I Z E 1:1 Stratification factors • ESR1 mutant (yes vs no) • Visceral disease (yes vs no) Treatment (N=560)
17 John G. Houston, Ph.D. President and Chief Executive Officer, Arvinas Conclusions
Continued efficacy and favorable tolerability put ARV-471 on a path to two pivotal studies beginning soon 18 • Favorable tolerability profile at 200 and 500 mg qd • At 200 mg phase 3 dose, no dose reductions and one discontinuation • ARV-471’s tolerability is well suited for development across the disease continuum Initiating Ph 3 trials • Monotherapy 2L Ph 3 in less treatment- experienced patients (Q4 2022) • Trial designed to address role in both ESR1mut and all-comers • Palbo combo 1L Ph 3 in patients with ER dependent tumors (Q1 2023) • Broader development initiated with other combos and in early breast cancer • ARV-471 demonstrates strong CBR and mPFS in heavily treatment-resistant patients • Activity in this difficult to treat population illustrates the potential of PROTAC technology TolerabilityEfficacy ARV-471 is an investigational compound. Its safety and efficacy has not been established aRate of confirmed complete response or partial response or stable disease ≥24 weeks CBR=clinical benefit rate; ER=estrogen receptor; ESR1=estrogen receptor 1 gene; PFS=progression-free survival
VERITAC data confirm ARV-471 has the potential to be a best-in- class ER-targeting therapy 19 ✓c ✓c ✓c ✓c ✓c ✓c 2020: Phase 1 PoC 2021: Phase 1 Readout 2022: Phase 2 Readout 2022: Planned initiation of TACTIVE-U, TACTIVE-E 2022: Planned initiation of TACTIVE-N 2022: Initiate Phase 1 in Japanese patients Validated PROTAC protein degrader Continued efficacy signals and favorable tolerability profile support advancement to Phase 3 registrational studies Phase 1 trial in Japan to enable global pathway Combination trials with multiple targeted therapies - on track to add additional agents to establish potential for ARV-471 as backbone therapy of choice Designed to evaluate safety and clinical activity in early breast cancer (e.g., neo-adjuvant) Next milestone: Two Phase 3 registrational studies (1L and 2L) Validated the evaluation of ARV-471 as a potential treatment for metastatic breast cancer
Q&A 20